This is a very early study with only 24 MSS CRC patients but the results are very encouraging. The more I look into it the more promising the results are and I felt the need to share this news.
In a nutshell the combination of Stivarga/regorafenib + Nivolumab had an Objective Response rate (tumor shrinkage of 30% and no new lesions) in 33% of MSS CRC patients (n=24). But that’s not all. If you look at the waterfall for CRC, 87% (21/24) of MSS CRC patients had stable disease, with only (5/24) having any significant lesion growth. Furthermore if you look at the waterfall for all patients, the best responders were on the lowest dose (80mg) and this is what’s recommended for further study. The standard dose for regorafenib (monotherapy) was 160mg, recently the Redos study showed starting at 80mg and escalating weekly to 160mg unless toxicity is reached is superior to the standard dose. This immunotherapy combination recommends using the lowest possible dose of regorafenib (and hence fewer side effects).
The biggest downside of this study is the short follow up (less than a year) duration so we don’t yet know if the responses are as durable in as say Pembrolizumab for MSI patients. But if you look at the spider plot for tumor response, it looks that at least for partial response patients the response may be somewhat durable. We’ll know more once the data matures, and I’m sure there will be many more studies looking into this. I think it’s fair to say this is by far the best response to immunotherapy in MSS we’ve seen.
Here is the best part. Regorafenib is already approved for advanced mCRC. Nivolumab or Keytruda are already on the market so any doctor can prescribe them right now, off label. (Nivolumab and Pembrolizumab are both Pd-1 inhibitors so they should be interchangeable). The main problem will be insurance reimbursement for the off-label immunotherapy. I’ve already heard of oncologists trying this with patients based on this study’s data. If I could handle Regorafenib and I had no other options, I would try this right now. If I have a therapy that’s working, I’d likely try to wait 6-12 months for more mature data, or tough it out until progression.


Regorafenib dose optimization study (ReDOS): Randomized phase II trial to evaluate dosing strategies for regorafenib in refractory metastatic colorectal cancer (mCRC)
https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.4_suppl.611